Exome-wide survey of the Siberian Caucasian population.

BACKGROUND: Population structure is an important factor in the genetic association studies but often remains underexplored for many human populations. We identified exome variants in 39 Siberian Caucasian individuals from Novosibirsk, Russia and compared their genetic allele frequencies with European populations from 1000 Genomes Project. METHODS: The study participants were from Novosibirsk and represented people with monogenic diabetes, healthy individuals and a cohort from the tick-borne encephalitis study. Isolated DNA was enriched using Agilent SureSelect V5 kit and sequenced on Illumina HiSeq 4000 and genetic variants were identified using GATK pipeline. To estimate the patterns of the population structure we used PCA and ADMIXTURE analysis. Pharmocogenetically and medically important variants were annotated based on PharmGKB and ClinVar databases. RESULTS: The analysis identified low, but highly significant population differentiation attributed to numerous loci between the Siberian Caucasian population and other European population samples as well as a higher proportion of the Finnish genetic component in the studied sample. The medical and pharmacogenetic annotation of highly significantly differentiated variants between the Novosibirsk and the combined European populations revealed a number of important genetic polymorphisms located in such genes as FCGR3B, TYR, OCA2, FABP1, CHEK2 and SLC4A1. CONCLUSIONS: The study reports for the first time an exome-wide comparison of a population from Russia with European samples and emphasizes the importance of population studies with medical annotation of variants.

Concerted changes in the nucleotide sequences of the intragenic promoter regions of eukaryotic genes for tRNAs of all specificities.

RNA polymerase III promoter is located within the coding region in all eukaryotic tRNA genes, whereas in prokaryotic tRNA genes, the promoter is located upstream of the transcription initiation site. We analyzed the nucleotide sequence context of the A and B boxes of RNA polymerase III promoters from different unicellular eukaryotes, plants, and animals and the homologous sequences in the tRNA genes of prokaryotic species (Archaea, Eubacteria). The long and short sequence variants of the A box are nonrandomly distributed across different types of the eukaryotic tRNA genes. In contrast, the sequences from the prokaryotic counterparts of the long and short variants are randomly scattered among prokaryotic tRNA genes. The sequence diversity of the 3' portion of the A box in the eukaryotic tRNA genes was sharply reduced compared to that of the homologous segments of the prokaryotic tRNA genes. Analysis of the frequencies of oligonucleotide variants from different parts of the A box suggested that the prominent changes in the structure of the A box occurred at about the same time in all tRNA genes during the prokaryote eukaryote evolutionary transition.